Nature has evolved mechanisms to create a diversity of specialized materials through nanoscale organization. Inspired by nature, hybrid materials are designed with highly tailorable properties, which are achieved through careful control of their nanoscale interactions. These novel materials, based on a silica‐gelatin hybrid system, have the potential to serve as a platform technology for human tissue regeneration. Covalent interactions between the inorganic and organic constituents of the hybrid are essential to enable the precise control of mechanical and dissolution properties. Furthermore, hybrid scaffold porosity is found to highly influence mechanical properties, to the extent where scaffolds of particular strength could be specified based on their porosity. The hybrids also demonstrate a non‐cytotoxic effect when mesenchymal stem cells are cultured on the material. Cytoskeletal proteins of the cells are imaged using actin and vimentin staining. It is envisaged these hybrid materials will find a diverse application in both hard and soft tissue regenerating scaffolds.

Clinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce host neovascularization at the graft surface, but hypoxic conditions cause cell death at the core. Addition of cellular components that generate an extensive primitive plexus-like vascular network that would perfuse the entire scaffold upon anastomosis could potentially yield significantly higher-quality grafts. We used a mouse model to develop a two-stage protocol for generating vascularized bone grafts using mesenchymal stem cells (hMSCs) from human bone marrow and umbilical cord-derived endothelial cells. The endothelial cells formed tube-like structures and subsequently networks throughout the bone scaffold 4–7 days after implantation. hMSCs were essential for stable vasculature both in vitro and in vivo; however, contrary to expectations, vasculature derived from hMSCs briefly cultured in medium designed to maintain a proliferative, nondifferentiated state was more extensive and stable than that with hMSCs with a TGF-β-induced smooth muscle cell phenotype. Anastomosis occurred by day 11, with most hMSCs associating closely with the network. Although initially immature and highly permeable, at 4 weeks the network was mature. Initiation of scaffold mineralization had also occurred by this period. Some human-derived vessels were still present at 5 months, but the majority of the graft vasculature had been functionally remodeled with host cells. In conclusion, clinically relevant progenitor sources for pericytes and endothelial cells can serve to generate highly functional microvascular networks for tissue engineered bone grafts.

Nanocomposite scaffolds of bioactive glass foams containing tailor made rare earth oxide (i.e. nanoceria) additives were demonstrated to enhance the production of collagen by HMSCs (Human Mesenchymal Stem Cells) compared to bioactive glass scaffolds without nanoceria. The addition of osteogenic supplements was not required for this to occur. Two different preparations of nanoceria were successfully incorporated in 3-D bioactive glass foam scaffolds and were compared with bioactive scaffolds without nanoceria. The nanoparticles had individual particle sizes of 3–5 nm while the agglomerate size varied from 5–15 nm. Preliminary investigations show that nanoceria is non toxic to the cells. After 10 days of culture, nanoceria containing scaffolds showed enhanced osteoblastic differentiation of HMSCs and collagen production compared to the scaffolds without nanoceria even in the absence of any osteogenic supplements (i.e. ascorbic acid, dexamethasone and β-glycerophosphate). This could be due to the incorporation of nanoceria, which acts as an oxygen buffer thereby regulating the differentiation of HMSCs. Further investigations are currently underway to determine the role of the nanoceria controlled oxygen buffering on the HMSC differentiation.